This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Reactivation of latent varicella zoster virus (VZV) leads to herpes zoster (HZ, shingles), which causes major morbidity and sometimes mortality in older individuals. Advanced age is the primary risk factor not only for developing HZ, but also complications such as post herpetic neuralgia. The currently approved vaccine against HZ reduces the incidence of shingles by only 51%. A major obstacle in developing better treatments and vaccines for HZ is that VZV infection of laboratory animals does not result in clinical disease. Consequently, our understanding of the immune correlates of protection against VZV infection and reactivation remains very limited. We have developed a nonhuman primate model wherein young rhesus macaques infected with simian varicella virus (SVV) display the hallmarks of VZV infection in humans. In contrast to young rhesus macaques, aged animals infected with SVV remain persistently viremic despite the development of an IgG antibody response that was comparable to that generated by young animals. On the other hand, SVV-specific T cell responses in aged animals were significantly delayed compared to those generated by young animals. These data strongly suggest that, as described for VZV, defects in T cell responses in aged animals result in poor immunological control of SVV replication. Therefore, SVV infection of young and aged rhesus macaques provides a unique opportunity to: (1) identify age-related differences in the SVV-specific T cell responses and (2) determine how these differences in immune responses affect the aged animal's ability to control SVV replication and to maintain latency.